Brucella spp. and Trypanosoma cruzi are two intracellular pathogens that have no evolutionary common origins but share a similar lifestyle as they establish chronic infections for which they have to circumvent the host immune response. Both pathogens have a virulence factor (prpA in Brucella and tcPrac in T. cruzi) that induces B-cell proliferation and promotes the establishment of the chronic phase of the infectious process. We show here that, even though PrpA promotes B-cell proliferation, it targets macrophages in vitro and is translocated to the cytoplasm during the intracellular replication phase. We observed that PrpA-treated macrophages induce the secretion of a soluble factor responsible for B-cell proliferation and identified nonmuscular myosin IIA (NMM-IIA) as a receptor required for binding and function of this virulence factor. Finally, we show that the Trypanosoma cruzi homologue of PrpA also targets macrophages to induce B-cell proliferation through the same receptor, indicating that this virulence strategy is conserved between a bacterial and a protozoan pathogen.
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http://dx.doi.org/10.1074/jbc.M113.453282 | DOI Listing |
Int J Biol Macromol
January 2025
School of Life Sciences, Zhengzhou University, Henan, Zhengzhou 450001, China; School of Advanced Agricultural Sciences, Peking University, Beijing 100000, China; Longhu Laboratory, Henan, Zhengzhou 450001, China; Henan Key Laboratory of Immunobiology, Henan, Zhengzhou 450001, China; College of Veterinary Medicine, Henan Agricultural University, Henan, Zhengzhou 450001, China. Electronic address:
Autoimmune diseases are characterized by dysregulated immune responses and chronic inflammation. B cell activating factor (BAFF) and interleukin-17 (IL-17) are key mediators in the pathogenesis of several autoimmune diseases, driving B cell hyperactivation, autoantibody production, and tissue damage. Simultaneous targeting of these pathways may provide a synergistic therapeutic approach.
View Article and Find Full Text PDFDev Comp Immunol
January 2025
Institute of Modern Aquaculture Science and Engineering, School of Life Sciences, South China Normal University, Guangzhou, 510631, China; Guangzhou Key Laboratory of Subtropical Biodiversity and Biomonitoring, Guangdong Provincial Engineering Technology Research Center for Environmentally-Friendly Aquaculture, South China Normal University, Guangzhou, 510631, China. Electronic address:
IL-21 is a type I cytokine that is produced by activated CD4 T cells and has a significant impact on the growth, survival, and functional activation of B lymphocytes. While IL-21 has been identified in several teleost fish species, its function and associated mechanisms focus on teleost fish B cells remain largely unknown. In this study, we aimed to investigate the effects of IL-21 (OnIL-21) on IgM B cells from Nile tilapia (Oreochromis niloticus), as well as the intracellular signaling transduction pathway involved.
View Article and Find Full Text PDFInt Immunol
January 2025
Division of Innate Immunity, The Institute of Medical Science, The University of Tokyo; Minato-ku, Tokyo 108-8639, Japan.
The cancer driver mutation L265P MyD88 is found in approximately 30 % of cases in the activated B cell-like subgroup of diffuse large B cell-like lymphoma (ABC DLBCL). L265P MyD88 forms a complex with TLR9 and IgM, referred to as the My-T-BCR complex, to drive proliferation. We here show that the B cell surface molecules CD19 and CD20 enhance proliferation mediated by the My-T-BCR complex.
View Article and Find Full Text PDFbioRxiv
January 2025
Department of Chemistry, 409 McCormick Road, University of Virginia, Charlottesville, VA 22904.
Antibody production is central to protection against new pathogens and cancers, as well as to certain forms of autoimmunity. Antibodies often originate in the lymph node (LN), specifically at the extrafollicular border of B cell follicles, where T and B lymphocytes physically interact to drive B cell maturation into antibody-secreting plasmablasts. In vitro models of this process are sorely needed to predict aspects of the human immune response.
View Article and Find Full Text PDFUnlabelled: X-linked Lymphoproliferative Syndromes (XLP), which arise from mutations in the or genes, are characterized by the inability to control Epstein-Barr Virus (EBV) infection. While primary EBV infection triggers severe diseases in each, lymphomas occur at high rates with XLP-1 but not with XLP-2. Why XLP-2 patients are apparently protected from EBV-driven lymphomagenesis, in contrast to all other described congenital conditions that result in heightened susceptibility to EBV, remains a key open question.
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